Bone morphogenic protein-9 stimulates endothelin-1 release from human pulmonary microvascular endothelial cells: A potential mechanism for elevated ET-1 levels in pulmonary arterial hypertension

Abnormalities of signalling for the transforming growth factor beta (TGFβ) family of peptides, including bone morphogenic proteins (BMP), have been described in heritable pulmonary arterial hypertension (PAH). TGFβ can modulate synthesis of the vasoconstrictor and mitogen, endothelin-1 (ET-1), a mediator that contributes to the pathogenesis of PAH. BMP-9 is a circulating peptide recently recognized to affect endothelial function. The stimuli for increased microvascular endothelial production of ET-1 in PAH are unknown. We therefore studied the effects of BMP-9 on ET-1 production by human lung blood microvascular endothelial cells (HMVEC-LBl) in vitro. In vitro, BMP-9 increased ET-1 production by HMVEC-LBl. The effect was identical to TGFβ-1, but BMP-9 and TGFβ-1 combined further increased ET-1 levels by 29%. As compared to TGFβ-1, BMP-9 induced more potent and rapid phosphorylation of Smad 1/5, the downstream signalling molecules of the activin-like kinase 1 (ALK-1) receptor. Moreover, as has been previously shown for endothelial cells of other origin, BMP-9 also induced Smad 2 phosphorylation in HMVEC-LBl. In conclusion, BMP-9 stimulates ET-1 production by HMVEC-LBl in vitro. BMP-9 signals via several Smad pathways. These studies provide novel mechanisms for the potentiation of PAH.     

心绞痛患者同型半胱氨酸和内皮素及血管性假血友病因子的改变

目的 :观察不稳定型心绞痛 (UAP)患者同型半胱氨酸 (Hcy)、内皮素 (ET)及血管性假血友病因子(vWF)的变化。方法 :UAP患者 34例、正常体检者 2 1例分别在清晨采血测定Hcy、ET及vWF值。 结果 :UAP患者Hcy、ET及vWF值均明显高于正常者 [(12 .2± 3.2 )∶(4 .9± 1.6 ) μmol/L、(12 9.3± 2 6 .4 )∶(85 .2± 39.6 )ng/L及 (185 .4± 32 .4 ) %∶(14 2 .1± 4 2 .0 ) % ,均P <0 .0 5 ],三者之间不具有相关性 (r =0 .18、0 .19、0 .15 ,均P >0 .0 5 )。结论 :Hcy、ET及vWF的改变可能参与UAP的病理生理过程。     

冠状动脉球囊成形术对冠脉循环中血管内皮细胞和内皮素含量的影响

观察 1 5例冠心病患者PTCA前后冠脉循环中内皮细胞、内皮素及前列环素的改变。结果 :( 1 )PTCA术后冠脉循环中内皮细胞数显著增高 ,在术后 6小时达高峰 (P <0 0 1 ) ,内皮素及前列环素含量明显升高 ,在术后 1 2小时达高峰 (P <0 0 1 )。 ( 2 )球囊扩张时间超过 4分钟比低于 2 5分钟的患者其内皮素及前列环素均增高 (P <0 0 5)。提示由于球囊机械刺激及缺血再灌注引起的内皮细胞损伤 ,可能与PTCA后继发冠脉收缩及血栓形成有关。     

慢型、潜在型克山病患者的血管内皮功能观察

目的观察山东省慢型、潜在型克山病患者的临床特点和血管内皮功能,探讨机体内皮功能失调与克山病发生发展的关系。方法选择慢型、潜在型克山病患者57人、病区健康人34人,分别采集清晨空腹血检测ET、NO、NOS、iNOS及cNOS含量及活性。结果(1)克山病患者ET水平明显高于病区健康人(P<0.01);心功能越差,ET升高越明显(P<0.01);(2)NO和NOS含量,潜在型、慢型克山病均明显高于病区健康人(P<0.01);慢型高于潜在型(P<0.01);iN-OS含量克山病患者也高于病区健康人(P<0.05);慢型克山病高于潜在型克山病(P<0.05)。结论ET、NO水平的变化可能作为一种中间环节参与了克山病的发病机制;心功能不同,血浆ET、NO升高的程度也不同;ET、NO可作为克山病病情严重程度的预测指标。     

波生坦与硝苯地平对脱氧皮质酮-盐敏感高血压鼠主动脉血管重塑的影响

目的:观察波生坦和硝苯地平对脱氧皮质酮(DOCA)-盐敏感高血压鼠(DHR)血压、主动脉结构、血浆内皮素-1(ET-1)和主动脉组织ET-1 mRNA表达的影响,探讨其可能的作用及其机制。方法:40只SD大鼠, 等分为正常对照组、DHR对照组、波生坦组和硝苯地平组,波生坦组给予波生坦100 mg·kg-1·d-1灌胃,硝苯地平组给予35 mg·kg-1·d-1灌胃,每周测尾动脉血压1次,4周后处死,抽取动脉血放射免疫法测血浆ET-1 浓度,取主动脉分别作病理分析和逆转录聚合酶链反应检测ET-1 mRNA表达。结果:DHR对照组血压明显升高,血管平滑肌细胞肥大,弹力纤维层增厚,中层厚度及中层厚度／内径明显增大。波生坦组血压上升幅度降低, 上述血管组织变化明显改善。硝苯地平可抑制DHR血压上升,血管组织变化与模型对照组相似。血浆ET-1浓度在DHR对照组、波生坦组和硝苯地平组均有显著升高,但以波生坦组升高更为显著;DHR对照组、波生坦组和硝苯地平组主动脉组织ET-1 mRNA表达与正常对照组相比,均有显著增加,但3组间差异无统计学意义。结论:波生坦可降低DHR上升的血压,改善主动脉重塑可能系波生坦阻断了ET-1与其受体结合的结果。硝苯地平能抑制DHR的血压升高,但不能改善主动脉的重塑。     

肺动脉高压治疗进展

肺动脉高压是一种进行性发展且预后不良的疾病.随着对肺动脉高压发病机制研究的不断深入,其治疗已从单纯的血管扩张剂治疗发展到以疾病的分子遗传基础为靶向的药物治疗.本文着重介绍有关肺动脉高压治疗方面的进展.     

G alpha(q)-coupled receptors in human atrium function through protein kinase C epsilon and delta

Cardiac G alpha(q)-coupled receptors (such as endothelin, angiotensin, and alpha1-adrenergic receptors) mediate cardiac inotropy and chronotropy, as well as the development of hypertrophy. These receptors signal through protein kinase C (PKC), a family of 12 isozymes including PKC alpha, beta I, beta II, gamma, delta, epsilon, theta, eta, lambda, iota, zeta, and mu. Of these PKC isozymes, alpha, beta II, gamma, epsilon, delta, and zeta have been implicated in signaling through cardiac G alpha(q)-coupled receptors in various animal models. However, the profile of which isozymes are activated by a given G alpha(q)-coupled receptor varies among animal species. Thus, these results can not be extrapolated to human heart. In this study, we examine PKC isozymes activated by three different G alpha(q)-coupled receptors in human atrial tissue. Live atrial appendages obtained from the operating room were sliced and treated with agonists of G alpha(q)-coupled receptors, and cellular redistribution of PKC isozymes was examined by immunoblotting. We find that stimulation of G alpha(q)-coupled receptors in human atrium activates PKC epsilon and delta only, under both acute (5 min) and longer (35 min) stimulations. Further, PKC epsilon and delta exhibit distinct subcellular redistribution patterns; while both translocate to the plasma membrane upon G alpha(q) stimulation, PKC delta also redistributes to mitochondria. We conclude that PKC epsilon and delta are the main PKC isozymes involved in G alpha(q)-mediated signaling in human atria.     

清热理气冲剂对实验性胆汁反流性胃炎大鼠血浆内皮素和降钙素基因相关肽的影响

目的 探讨清热理气冲剂对实验性胆汁反流性胃炎（BRG）大鼠血浆内皮素（ET）和降钙素基因相关肽（CGRP）的影响。方法 60只大鼠随机分为A组（中药等效剂量组），B组（中药大剂量组），C组（西沙必利等效剂量组），D组（枸橼酸铋钾等效剂量组），E组（病理对照组）和F组（正常对照组）。除F组外，其余各组大鼠应用胆汁灌胃导致胃黏膜损害。2W后分别应用清热理气冲剂等效剂量、大剂量、西沙必利、枸橼酸铋钾处理。实验第4周观察胆汁反流性胃炎胃黏膜病理形态和应用放免法测定血浆ET和CGRP含量。结果 F组可见黏膜下层充血水肿，胃小凹增生，肠上皮化生，炎性细胞浸润等，而A组和B组胃黏膜组织形态显著改善。F组电镜观察到胃黏膜细胞问的紧密连接受损，线粒体肿胀，粗面内质网扩张，微绒毛变短或丢失，A组和B组的超微结构明显的改善。A组和B组血浆ET明显低于E组（P〈0．01）。A组和B组血浆CGRP明显高于E组（P〈0．01）。结论 清热理气冲剂可以减轻胃黏膜损伤，通过影响血浆ET和CGRP相关肽含量而达到治疗BRG目的。